Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma.

OBJECTIVE: To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). METHODS: A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. RESULTS: Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. CONCLUSIONS: FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.

Evaluation of the significance of interleukin-6 in the diagnosis of postoperative pneumonia: a prospective study.

BACKGROUND: Postoperative pneumonia (PP) is one of the most common complications after cardiac surgery. This study was designed to access the diagnostic value of interleukin-6 (IL-6) for pneumonia within the first 5 days after cardiac surgery in adults. METHOD: This prospective observational study enrolled 694 patients who admitted to our center from 10 October 2020 to 30 June 2021. Blood samples were collected after admission and on five consecutive days after surgery to measure IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) respectively. Combined with clinical data, we assessed the diagnostic performance of different biomarkers using univariate and multifactorial analyses as well as receiver operating characteristic curves (ROC) and the area under the curve (AUC). RESULT: Finally, 68 patients were diagnosed with PP (PP Group). In addition, 626 cases were assigned to the control group (Non-PP Group). From postoperative day 1 (POD1) to day 5, IL-6 and PCT levels showed higher diagnostic value (P < 0.001, P < 0.05, respectively); meanwhile, there was no difference in white blood cell counts between the two groups; CRP showed some value from POD2 onwards (P < 0.001). Among these biomarkers, IL-6 on POD1 [AUC: 0.78, 95% confidence interval (CI): 0.71-0.83], IL-6 on POD2 (AUC: 0.77, 95% CI: 0.71-0.82) and CRP levels on POD3 (AUC: 0.77, 95% CI: 0.70-0.84) had the highest diagnostic value. Multivariate analysis found that smoking status [odds ratio(OR): 7.79, 95% CI: 3.05, 19.88, p < 0.001], drinking status (OR: 22.68, 95% CI: 9.29, 55.37, p < 0.001) and hypertension (OR: 2.85, 95% CI: 1.28, 6.35, p = 0.011), IL-6 on POD2 (OR: 1.01, 95% CI: 1.00, 1.01, p = 0.018), mechanical ventilation time (OR: 1.03, 95% CI: 1.00, 1.05, p = 0.040) and intensive care unit stay time (OR: 1.01, 95% CI: 1.00, 1.02, p < 0.001) were independent risk factors for postoperative pneumonia. CONCLUSION: Smoking, drinking, hypertension, prolonged duration of mechanical ventilation and intensive care unit stay, and IL-6 on POD2 were independent risk factors for pneumonia after cardiovascular surgery. IL-6 level on POD2 may serve as a promising indicator, better than WBC, PCT and CRP.

Early postoperative calcitonin-to-preoperative calcitonin ratio as a predictive marker for structural recurrence in sporadic medullary thyroid cancer: A retrospective study.

Background: Calcitonin (Ctn) is widely used as a marker in the diagnosis, prognosis, and postoperative follow-up of patients with medullary thyroid carcinoma (MTC). The prognostic value of postoperative calcitonin-to-preoperative calcitonin ratio (CR), reflecting the change in Ctn level of response to initial treatment, remains uncertain in long-term disease outcomes. This study aims to determine the cut-off value of CR for predicting structural recurrence and assess the prognostic role of CR in patients with MTC. Methods: We retrospectively reviewed patients with MTC in Sun Yat-sen University Cancer Center (SYSUCC) between 2000 and 2022. CR is defined as the ratio of postoperative Ctn level on the day of discharge divided by preoperative Ctn level. In order to determine the optimal cut-off value of CR, the receiver operating characteristic (ROC) analysis was performed. We evaluate the effect of CR on recurrence-free survival (RFS) by using the Kaplan-Meier method and Cox regression analysis. Then, a nomogram based on CR was constructed. Results: In total, 112 sporadic MTC patients were included in this study. The optimal cut-off value of CR that predicted disease recurrence was 0.125. Patients with CR≥0.125 showed significantly worse RFS than patients with CR <0.125, respectively (3-years RFS rate of 63.1 vs. 94.7%, 5-years RFS rate of 50.7 vs. 90.3%, P < 0.001). In the multivariate analysis, CR was the strongest independent predictor of structural recurrence (HR: 5.050, 95% CI: 2.247-11.349, P <0.001). Tumor size (HR: 1.321, 95% CI: 1.010-1.726, P =0.042), multifocality (HR: 2.258, 95% CI: 1.008-5.058, P =0.048) and metastasized lymph nodes (HR: 3.793, 95% CI: 1.617-8.897, P <0.001) were also independent predictors of structural recurrence. The uncorrected concordance index (c-index) of the nomogram was 0.827 (95% CI, 0.729-0.925) for RFS, and bias-corrected c-index were similar. As compared to TNM stage, the nomogram based on CR provided better discrimination accuracy. Conclusions: We demonstrate that CR is a strong prognostic marker to predict structural recurrence in patients with sporadic MTC. The nomogram incorporating CR provided useful prediction of RFS for patients with sporadic MTC to provide personalized treatment.

Determinants of remission in a case series of medullary thyroid carcinoma

Background/aim: We aimed to present the clinical results of patients with medullary carcinoma under follow-up in our center and to determine parameters affecting remission and lymph node metastases. Material and methods: A retrospective analysis was performed of the medical records of 27 patients with MTC who were followed up between 2004 and 2020. Results: The mean age at diagnosis was 47.7 ± 14 years. The mean follow-up was 7.29 ± 4.9 years. Metastatic neck lymphadenopathy was detected in eight (29.6%) patients; none had distant metastasis at the time of diagnosis. The median tumor diameter was 1.50 (range: 0.4­6) cm. The median postoperative calcitonin level was 3.3 (range, 0.5­871) ng/L. Relapse occurred in 2 (range, 1­14) years after the first surgery in three (11.1%) patients. In the last visit, 7 (25.9%) patients had a structural incomplete response, and three (11.1%) patients had a biochemical incomplete response. Seventeen (59.3%) patients were in remission, no patients died of MTC or any other cause. Elevated postoperative calcitonin level was a significant prognostic parameter for remission (p = 0.12) and lymph node metastasis (p < 0.001). Conclusion: Elevated postoperative calcitonin level and perithyroid soft tissue invasion were significant prognostic parameters for remission and lymph node metastasis. Postoperative calcitonin level and calcitonin doubling time should be considered for prognostic and survival risk assessments.

[Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with tumorlet formation: A case report and review of the literature]. / Hiperplasia difusa idiopática de células neuroendocrinas pulmonares con formación de tumorlets: presentación de un caso clínico y revisión de la literatura.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is an infrequent lesion recently classified by the WHO as preinvasive. It can present with the formation of tumorlets (neuroendocrine cell groups up to 5 mm) which result in a typical histological and radiological image. We report a case of a 67-year-old women who presented with a chronic cough. The CT scan showed bilateral minute, multiple pulmonary nodules. A biopsy revealed a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with several tumorlets. After two years of follow-up, imaging studies showed no significant changes.

Diagnostic value of [18F]Fluorocholine PET/CT in detection of primary medullary thyroid cancer.

OBJECTIVE: Medullary thyroid cancer (MTC) is a challenging neuroendocrine malignancy where the role of nuclear medicine imaging is currently limited. This paper investigates the potential diagnostic value of [18F]Fluorocholine PET/CT in primary MTC. METHODS: We prospectively enrolled 25 patients (10 male, 15 female) with suspicion for primary MTC based on fine-needle aspiration biopsy (FNAB). All patients had a baseline three phase [18F]Fluorocholine PET/CT (2.5 MBq/kg): two regional head and neck and upper mediastinum studies at 5 min (first phase) and 120 min (third phase) and a whole-body PET/CT (from the skull vertex to mid-thighs) at 60 min (second phase). Any non-physiological radiotracer uptake was regarded as MTC positive. All patients referred to surgery had a preoperative neck-US. True lesion status was assessed using either histopathology, FNAB results or follow-up imaging and laboratory (calcitonin, CEA) results. Results with p < 0.05 were considered statistically significant. RESULTS: Nineteen of 25 patients (76%) were surgically treated and histopathology reports were obtained. Patient-based sensitivity and positive predictive value for detection of any MTC lesion using [18F]Fluorocholine PET/CT were both 100%. Neck-US was more specific (100% vs 70%; p = 0.002) and had a higher positive predictive value than [18F]Fluorocholine PET/CT (100% vs 55%; p = 0.018) for N1a and N1b staging. [18F]Fluorocholine PET/CT had a higher sensitivity (100% vs 50%; p = 0.025) and higher negative predictive value (100% vs 81%; p = 0.026) than neck-US for N1b staging. The optimal SUVmax cut-off to differentiate malignant from benign neck lesions at 60 and 120 min was 2.56. Patients with M1 stage on PET/CT had higher calcitonin (median of 5,372 vs 496.6 pg/ml; p = 0.005) and CEA concentrations (median of 95.8 vs 18.65 µg/l; p = 0.034) compared to patients with M0 disease. CONCLUSION: [18F]Fluorocholine PET/CT appears to be a promising radiotracer for primary staging of MTC by increasing diagnostic accuracy for N staging and detecting possible distant metastatic sites at initial presentation of disease.

Calcitonin negative medullary thyroid cancer in ectopic thyroid tissue: a rare diagnosis in an unusual location.

Medullary thyroid cancer is an aggressive form of thyroid cancer arising from parafollicular C cells. Calcitonin (CT) is a specific and sensitive biochemical marker which typically aids primary diagnosis and disease surveillance following treatment. There are rare cases of calcitonin negative medullary thyroid cancer (CNMTC) documented in the literature; however, to our knowledge, this case is the first report of CNMTC arising in ectopic thyroid tissue. We report a case of a 45-year-old man who attended his primary care physician with painless anterior neck swelling. In the absence of CT secreting disease, we have demonstrated the investigative process and the importance of immunohistochemical analysis to achieve a diagnosis. We also consider the challenges of monitoring disease recurrence in the absence of reliable biochemical markers.

Impurities identification and quantification for calcitonin salmon by liquid chromatography-high resolution mass spectrometry.

Calcitonin salmon is an important peptide pharmaceutical, which is mainly used for the treatment of osteoporosis and hypercalcemia. Structurally related peptide impurities in a peptide pharmaceutical probably have side effect or even toxicity, thus needs to be carefully characterized according to pharmacopoeia. With the improvement of analytical techniques, liquid chromatography-high resolution mass spectrometry (LC-HRMS) has become a pivotal technique for the identification and quantification of structurally related peptide impurities in peptide materials. In this study, an LC-HRMS-based method has been developed for the identification and quantification of structurally related peptide impurities in calcitonin salmon material. With this method, 7 peptide impurities (> 1 mg/g) in United States Pharmacopoeia (USP) reference standard and 9 peptide impurities (> 1 mg/g) in European Pharmacopoeia (EP) reference standard were identified and accurately quantified. Besides the peptide impurities reported by USP and EP, several new impurities such as [7-Dehydroalanine] calcitonin salmon, triple-sulfate-calcitonin salmon, [26-Proline] calcitonin salmon, [14-Glutamic acid] calcitonin salmon, [20-Glutamic acid] calcitonin salmon, [26-Aspartic acid] calcitonin salmon, calcitonin salmon acid were observed in the reference standard materials studied. The total mass fractions of all structurally related peptide impurities in calcitonin salmon study materials were estimated to be 57.4 mg/g for USP and 46.3 mg/g for EP with associated expended uncertainties at a 95 % confidence level of 5.2 mg/g (k = 2) and 3.1 mg/g (k = 2), respectively.

Calcitonin levels by ECLIA correlate well with RIA values in higher range but are affected by sex, TgAb, and renal function in lower range.

Calcitonin (CT) is a marker for both initial diagnosis and monitoring of patients with residual or recurrent medullary thyroid carcinoma (MTC). In Japan, serum CT had been measured by radioimmunoassay (RIA) until recently. Electrochemiluminescence immunoassay (ECLIA) became commercially available in 2014, and this technique is now the only method used to examine CT concentration. The purposes of this study were to investigate the correlations between the CT concentration measured with ECLIA (ECLIA-CT) and RIA (RIA-CT) and to explore the clinical characteristics of patients with elevated ECLIA-CT. CT concentrations of 348 sera samples from 334 patients with various thyroid disorders including nine MTC were measured using both assays. The correlation analysis revealed an excellent correlation between ECLIA-CT and RIA-CT among the cases with CT level >150 pg/mL by both assays (rs = 0.991, p < 0.001). However, 63% of all samples exhibited undetectable ECLIA-CT, while their RIA-CTs were measured between 15 and 152 pg/mL. The ECLIA-CTs in all patients who underwent total thyroidectomy for non-MTC showed low concentrations. High ECLIA-CT was observed in patients with MTC or pancreas neuroendocrine tumor. ECLIA-CT was also increased in 14 other male patients with non-MTC, including four with renal failure. Multivariate logistic regression analysis showed that male sex, negative TgAb, and lower estimated glomerular filtration rate were independent factors to predict detectable ECLIA-CT (≥0.500 pg/mL). These results indicate that ECLIA-CT correlates well with RIA-CT in higher range and is affected by sex, TgAb, and renal function.

A ratiometric electrochemiluminescent immunoassay for calcitonin by using N-(aminobutyl)-N-(ethylisoluminol) and graphite-like carbon nitride.

A ratiometric electrochemiluminescent (ECL) assay is described for the determination of the calcium(II) regulator calcitonin (CT). The method is making use of (a) graphite-like carbon nitride (g-C3N4) as the cathodic luminophore, (b) N-(aminobutyl)-N-(ethylisoluminol) (ABEI) as the anodic luminophore, and (c) peroxodisulfate and dissolved oxygen as coreactants. The luminous potential of g-C3N4 and ABEI can be well distinguished because of their different luminescent properties. Energy transfer between g-C3N4 and ABEI is not observed, and the coreactants peroxodisulate and oxygen do not interfere with each other. Au nanoparticles were functionalized with g-C3N4 and placed on the electrode to serve as a matrix for immobilization of primary antibody (Ab1). In the presence of CT, it will bind to the electrode. Then secondary antibody (Ab2) modified with polyaniline (PANI) and ABEI is incubated onto the electrode. With the increase in the concentration of CT, the blue ECL of g-C3N4 is quenched by PANI, while the blue luminescence of ABEI is enhanced. This enables ratiometric detection of calcitonin by ratioing the internsities at 460 and 475 nm. Response is linear in the 0.1~40 pg·mL-1 CT concentration range, and the limit of detection is 23 fg·mL-1. The method breaks the limitation of common ECL ratiometric strategy, namely, two luminophores often share the common coreactant. Graphical abstractSchematic representation of an immunoassay where polyaniline (PANI) in a BSA-Ab2-ABEI-Au@PANI composite quenches the cathodic signal of a graphitic carbon nitride (Au-g-C3N4) modified with gold nanoparticles (Au), while N-(aminobutyl)-N-(ethylisolumino) (ABEI) in the BSA-Ab2-ABEI-Au@PANI composit produces an anodic signal that enables quantitation of calcitonin.

Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers.

BACKGROUND: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care. METHODS: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model. RESULTS: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics. CONCLUSIONS: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.

A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection.

Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42-0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82-0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23-43.26] for a 400 mg/µg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/µg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/µg cutoff, 2.26-13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.

Changes in Serum Calcitonin Concentrations, Incidence of Medullary Thyroid Carcinoma, and Impact of Routine Calcitonin Concentration Monitoring in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL).

OBJECTIVE: Increases in serum calcitonin, a tumor marker for medullary thyroid carcinoma (MTC), have been associated with glucagon-like peptide 1 receptor agonist use in some preclinical studies. We report calcitonin changes in exenatide-treated and placebo-administered participants and MTC incidence in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and consider the impact of within-trial calcitonin monitoring. RESEARCH DESIGN AND METHODS: EXSCEL participants were randomized 1:1 to once-weekly exenatide 2 mg or placebo. Serum calcitonin was measured at baseline (with trial medication discontinued if >40 ng/L) and annually thereafter (with trial medication discontinued if ≥50 ng/L). Median calcitonin concentrations were calculated at each time point, and thyroid malignancies were collected prospectively. Data regarding follow-up after an elevated calcitonin were collected retrospectively. RESULTS: At baseline, 52 (30 exenatide and 22 placebo) participants had calcitonin >40 ng/L, and during follow-up an additional 23 participants (15 exenatide and 8 placebo) had calcitonin ≥50 ng/L in the intention-to-treat population. Median calcitonin concentrations were similar between treatment groups at baseline with no increase over time. Confirmed MTC occurred in three participants (2 exenatide and 1 placebo), all of whom had significantly elevated baseline calcitonin values (413, 422, and 655 ng/L). CONCLUSIONS: During a median 3.2 years' follow-up, no change in serum calcitonin was seen with exenatide therapy. The three confirmed cases of MTC all occurred in participants with markedly elevated baseline calcitonin levels, measured prior to trial medication administration. Regular calcitonin monitoring identified no additional cases of MTC, suggesting no benefit of routine calcitonin monitoring during exenatide treatment.

Expression of Prox1 in Medullary Thyroid Carcinoma Is Associated with Chromogranin A and Calcitonin Expression and with Ki67 Proliferative Index, but Not with Prognosis.

Medullary thyroid carcinoma (MTC) has been shown to express Prospero homeobox protein 1 (Prox1), a transcription factor whose expression is altered in a variety of human cancers. We conducted a retrospective study on a series of 32 patients with MTC to test the correlation of Prox1 expression in MTC with clinicopathological features and to evaluate its prognostic significance. Correlation of Prox1 immunohistochemical expression with tumor size, proliferative index (Ki67), and calcitonin and CEA serum levels prior to surgery was tested for significant correlations. The difference in Prox1 and Ki67 immunohistochemical expression according to the immunohistochemical staining intensity of CEA, chromogranin A, and calcitonin was tested using the Kruskal-Wallis H test and linear regression analysis. The prognostic value of Prox1 and Ki67 for our patient cohort was assessed by Kaplan-Meier log rank survival analysis. We demonstrated a positive correlation between Prox1 expression and Ki67 index. Prox1 also showed significant difference in expression according to chromogranin A and calcitonin immunohistochemical expression, with higher Prox1 expression in tumors with stronger chromogranin A or calcitonin staining. Prox1 expression did not correlate with PFS or OS based on Kaplan-Meier log rank survival analysis. In conclusion, Prox1 expression in MTC is positively correlated with Ki67 and with the immunohistochemical expression of chromogranin A and calcitonin. However, the present study does not support a role for Prox1 in MTC prognosis.

Evaluation of procalcitonin immunoassay concordance near clinical decision points.

Background Procalcitonin (PCT) is a biomarker for systemic bacterial infections and may aid in decision making for antimicrobial stewardship. Numerous PCT assays are available on common clinical immunoassay platforms. However, questions remain about the harmonization of these assays and whether the same clinical decision points may be used with all methods. Methods Thirty-seven remnant patient serum samples were analyzed across four different PCT assays: Abbott ARCHITECT i2000, bioMérieux MINI VIDAS, Roche Elecsys cobas e 411, and BRAHMS KRYPTOR. Regression analysis was performed, and correlation was assessed at common clinical decision points for antimicrobial therapy: 0.10, 0.25, and 0.50 µg/L. Results Data showed a positive bias of the MINI VIDAS compared to the KRYPTOR (slope=1.188, R=0.9873) and negative biases of both the ARCHITECT i2000 and cobas e 411 compared to the KRYPTOR (slope=0.806, R=0.8864, and slope=0.795, R=0.8974, respectively). A comparison of results at commonly used clinical decision points for antimicrobial stewardship showed that, relative to the KRYPTOR, 21% of samples would be classified into different interpretive categories by the ARCHITECT i2000 method, 31% of samples would be classified differently by the MINI VIDAS method, and 16% of samples would be classified differently by the cobas e 411 method. Conclusions All methods showed reasonable analytical agreement; however, an analysis of result interpretation at clinical decision points showed that many samples were differentially categorized (e.g. shifted by one interpretive category) by the methods. Overall, our findings support a need for harmonization of PCT methods. Until then, institutions should independently evaluate their PCT assays against predicate methods and consider the impact on result interpretation prior to incorporating PCT into clinical practice.

C-cell hyperplasia in sporadic and familial medullary thyroid carcinoma.

CONTEXT: C-cell hyperplasia (CCH) is characterized by increased mass of C-cells and has been identified as a precursor condition for medullary thyroid carcinoma (MTC). Varying proportion of MTCs is associated with CCH in different studies. This could be due to the lack of uniformity of the definitions and techniques used to identify CCH in these studies. AIMS: This study aims to study the occurrence, clinicopathological, and immunohistochemical features of CCH in MTC diagnosed during a 22-year period at a tertiary care center in North India and to review the available literature on CCH. MATERIALS AND METHODS: Eighty-seven consecutive cases of MTC were included in the study. Histological evaluation for the presence of CCH and neoplastic CCH was performed. Confirmation of CCH was done by immunohistochemistry for calcitonin and chromogranin. The presence of neoplastic CCH was correlated with clinical factors and prognostic factors. RESULTS: Of 87 cases of MTC included in the study, 71 (82%) patients were sporadic and 16 (18%) had familial MTC. Neoplastic CCH was seen in 12 (75%) familial and in 9 (13%) sporadic MTC. Patients with familial MTC were more frequently associated with neoplastic CCH than sporadic MTC (P < 0.001), were younger (P < 0.001), and had more often bilateral and multifocal tumors (P < 0.001). However, there was no significant difference in mean survival time and progression-free survival in patients with and without CCH. CONCLUSION: CCH, though more common in familial MTC, can also be seen in sporadic tumors. CCH is not associated with patient survival and disease progression.

Role of C-reactive protein and procalcitonin in discriminating between infectious fever and tumor fever in non-neutropenic lung cancer patients.

This study assessed whether C-reactive protein (CRP) and procalcitonin (PCT) levels can discriminate between infectious fever and tumor fever (TF) in non-neutropenic patients with nonsmall cell lung cancer (NSCLC).This retrospective clinical study included 96 adults with NSCLC who were admitted to the Third Hospital of Hebei Medical University between July 2015 and July 2017. Febrile, non-neutropenic patients were enrolled. CRP and PCT levels, neutrophil count, and antimicrobial response were evaluated.This study included 26 patients with TF, 49 with localized bacterial infection (LBI), and 21 with bloodstream infection (BSI). CRP levels in BSI were significantly higher than in TF (P < .05) and LBI (P < .05). No statistically significant difference was found between patients with TF and LBI (P > .05). PCT levels were significantly higher in BSI and LBI than in TF (P < .05). CRP and PCT levels in patients with stage IV disease were significantly higher than in those with stage II to III disease (P < .05). CRP and PCT levels declined significantly in patients with BSI who were responding to antimicrobials (P < .05).Compared with CRP levels, PCT levels can discriminate between TF and infectious fever more accurately. PCT and CRP levels may predict different stages of lung cancer.

Diagnostic and prognostic properties of procalcitonin in patients with acute dyspnea: Data from the ACE 2 Study.

BACKGROUND: Procalcitonin (PCT) concentrations increase during bacterial infections and could improve diagnosis of pneumonia and risk stratification in patients with acute dyspnea. METHODS: PCT concentrations were measured <24 h of admission in 310 patients with acute dyspnea and compared to C-reactive protein (CRP) and white blood cells (WBC) in the total cohort and the subset of patients with concomitant acute heart failure (HF). RESULTS: We diagnosed pneumonia in 16 out of 140 patients with acute HF (11%) and in 45 out of 170 patients with non-HF-related dyspnea (27%). PCT concentrations were higher in patients with pneumonia vs. patients without pneumonia, both among acute HF patients (median 2.79 [Q1-3 0.18-5.80] vs. 0.10 [0.07-0.14] ng/mL, p < .001) and non-HF patients (0.22 [Q1-3 0.13-0.77] vs. 0.07 [0.05-0.10] ng/mL, p < .001). CRP and WBC were also higher in patients with pneumonia in both groups, but among acute HF patients, only PCT concentrations were associated with pneumonia in multivariate analysis. In patients with acute HF, receiver-operating statistics area under the curve (ROC-AUC) to diagnose pneumonia was 0.90 (95% CI 0.81-0.98) for PCT, 0.84 (0.73-0.94) for CRP, and 0.72 (0.57-0.87) for WBC. The corresponding ROC-AUCs among patients with non-HF-related dyspnea were 0.88 (0.82-0.93), 0.94 (0.90-0.98), and 0.79 (0.72-0.87), respectively. During a median follow-up of 823 days (Q1-3 471-998) 114 patients died, and PCT and CRP, but not WBC concentrations were associated with all-cause mortality. CONCLUSION: In acute HF patients, PCT concentrations were superior to CRP and WBC to diagnose concurrent pneumonia.

In situ enzymatic generation of gold for ultrasensitive amperometric sandwich immunoassay of procalcitonin.

Procalcitonin (PCT) is an important indicator for bacterial inflammatory diseases, and its sensitive, accurate and rapid detection has important clinical value. On the basis of sandwich immunoassay, glucose oxidase-catalyzed gold deposition and in-situ microliter-droplet anodic stripping voltammetry (ASV) of the enzyme-generated gold directly on the immunoelectrode, the ultrasensitive electrochemical detection of PCT is achieved. A new method of the chemical dissolution of gold by an appropriately diluted aqua regia and the simultaneous cathodic preconcentration of gold on the immunoelectrode is suggested, which gives the better performance for the ASV analysis of gold than the reported one. Under optimized conditions, the ASV peak current is linear with the common logarithm of PCT concentration from 0.05 fg mL-1 to 500 ng mL-1, with a limit of detection (LOD, S/N = 3) as low as 0.04 fg mL-1. Our method has also been used for detection of PCT in serum samples with satisfactory results.

Predictive value of PCT and IL-6 for bacterial infection in children with cancer and febrile neutropenia.

PURPOSE: Only a third of children with cancer and febrile neutropenia (FN) have a proven bacterial infection; nevertheless, most children are hospitalized and treated with intravenous antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We aimed to evaluate the role of interleukin-6 (IL-6) and procalcitonin (PCT) in diagnosing bacterial infection in children with cancer and FN. METHODS: The study population was derived from a prospective database (2006-2013, IL-8 study) comprising children with cancer who presented with FN. From stored plasma samples (taken at admission and/or at 12-24 h), we determined the PCT and IL-6 levels. Consequently, we explored their relation with the presence of bacterial infection (positive blood culture, radiologically documented infection or clinical bacterial focus). We predefined cutoff values at 60 ng/L for IL-6 and 0.25 ng/mL for PCT. RESULTS: Seventy-seven FN episodes in 55 children with cancer were included. In 18 episodes (23.4%), a bacterial infection was documented. Both at presentation and after 12-24 h, median values of IL-6 and PCT were significantly higher in patients with a bacterial infection compared to patients without a bacterial infection. With both biomarkers above cutoff values, sensitivity was 93% (with either one, this was even 100%). The identified group at low risk for bacterial infection comprised 41% of the population. CONCLUSION: PCT and IL-6 are promising markers in identifying bacterial infection in children with cancer and FN. In a subsequent project, we will incorporate these biomarkers in a risk assessment model that we will test prospectively in a clinical trial.